DE102008009039A1 - New compounds from Antrodia camphorata - Google Patents

Abstract

The present invention relates to a novel compound and its use, in particular Antroquinonol B and Antroquinonol C, which have been isolated from Antrodia camphorata extracts and which can effectively inhibit the growth of cancer cells. The compounds of Antrodia camphorata first described can be used not only to inhibit the growth of breast cancer, lung cancer, liver cancer and prostate cancer, but also in medical anticancer compositions for the above-mentioned cancer cells.

Description

Background of the invention

1. Field of the invention

The The present invention relates to compounds and their use, in particular antroquinonol B and antroquinonol C compounds, which have been isolated from Antrodia camphorata extracts, and their use for growth inhibition of tumor cells. It will first described compounds from Antrodia camphorata that are not only to inhibit the growth of breast cancer, lung cancer, liver cancer and prostate cancer can be used, but also in medicinal anticancer compositions for the above called cancer cells.

2. State of the art

Antrodia camphorata is also called Chang-Zhi, Niu Chang-zhi, red camphor mushroom and the like, and is a perennial fungus, which belongs to the order Aphyllophorales, family Polyporaceae. It is an endemic species in Taiwan that is found on the inner, rotten heartwood wall of Cinnamomum kanehirae Hay is growing. Cinnamomum kanehirae Hay rarely occurs and becomes illegally excessive harvested, causing Antrodia camphorata, which is wild within the Baums grows, even become rare. Because the growth speed from natural Antrodia camphorata, only from June to October is growing, extremely low, is the price of Antrodia camphorata very high.

The Fruit bodies of Antrodia camphorata are perennial, Unstained, hard and woody and give a strong smell of sassafras (Camphor aroma). The appearance is varied and has plate-like, bell-like, hoof-like or tower-like forms. They point a reddish color and are flat when young, and adhere to the surface of wood. Then the Margins of the front end slightly wavy and lean and extend into the environment. The color changes turning into a pale reddish-brown or a creamy yellow-brown around, with oysters everywhere. This area is of very high medical value.

In Traditional Taiwanese medicine becomes Antrodia camphorata commonly used as antidote, liver protectants and anticancer agents used. Antrodia camphorata is as generally edible and medicinal Mushrooms rich in numerous nutrients, including Triterpenoids, polysaccharides (such as β-glucosan), Adenosine, vitamins (such as vitamin B, nicotinic acid), Proteins (immunoglobulins), superoxide dismutase (SOD), trace elements (such as calcium, phosphorus and germanium, etc.), nucleic acids, Steroids and blood pressure stabilizers (such as antidia acid) and the same. It is assumed that these are physiological active ingredients z. B. have the following effects: antitumor activities, an increase in immunomodulating activities, antiallergic effects, antibacterial effects, a blood pressure reduction, a lowering of blood sugar, cholesterol lowering and the like.

Triterpenoids are the most intensively studied component of the numerous compositions of Antrodia camphorata. Triterpenoids is the generic term for natural compounds containing 30 carbon atoms with pentacyclic or hexacyclic structures. The bitter taste of Antrodia camphorata is due to the triterpenoid component. Three new ergostane-type triterpenoids (Antcin A, Antcin B, Antcin C) have been described by Cherng et al. isolated from the fruiting bodies of Antrodia camphorata ( IH Cherng and HC Chiang, 1995, Three new triterpenoids from Antrodia cinnamomea, J. Nat. Prod., 58, 365-371 ). Three new compounds, known as "Zhankuic" acid A, "Zhankuic" acid B and "Zhankuic" acid, have been reported by Chen et al. extracted from the fruiting bodies of Antrodia camphorata with ethanol ( CH Chen and SW Yang, 1995, New steroid acids from Antrodia cinnamomea - a fungus parasitic to Cinnamomum micranthum, J. Nat. Prod. 58, 1655-1661 ). In addition, have Cherng et al. also found three other novel triterpenoids from the fruiting bodies of Antrodia camphorata which are sesquiterpene lactone and 2-biphenyl derived compounds, 4,7-dimethoxy-5-methyl-1,3-benzodioxole and 2,2 ', 5' , 5'-tetramethoxy-3,4,3 ', 4'-bi-methylenedioxy-6,6'-dimethylbiphenyl ( HC Chiang, DP Wu, IW Cherng and CH Ueng, 1995, sesquiterpene lactones, phenyl and biphenyl compounds from Antrodia cinnamomea, Phytochemistry, 39, 613-616 ). In 1996, four new ergostane-type triterpenoids (Antcine E and F and Methylantcinate G and H) were obtained from Cherng et al. isolated by the same analytical methods ( IH Cherng, DP Wu and HC Chiang, 1996, Triterpenoids from Antrodia cinnamomea, Phytochemistry 41, 263-267 ). Two ergostane-related steroids, "Zhankuic" acids D and E, were co-administered with three lanostane-related triterpenes, 15-alpha-acetyldehydrosulfuric acid, Dehydroeburi coconut acid, dehydrosulfuric acid, from Yang et al. isolated ( SW Yang, YC Shen and CH Chen, 1996, Steroids and triterpenoids of Antrodia cinnamomea - a fungus parasitic to Cinnamomum micranthum, Phytochemistry 41, 1389-1392 ).

Even though based on previous experiments (such as those above cited by Chen and Yang, 1995) that Antrodia camphorata extracts have anti-tumor effects, Further experiments are needed to get the effective composition to identify for tumor inhibition. The application in cancer therapy will have very beneficial effects when the actual effective compositions found become.

Summary of the invention

In order to identify the compounds having antitumor effects in the extracts of Antrodia camphorata, the compound of formula (1) was isolated and purified in the present invention, wherein x may be hydroxyl (-OH) or methoxy (-OCH ₃ ).

When x is hydroxyl, the structure is as shown in the formula (2). The chemical name is Antrochinonol B, which has the molecular formula C ₂₄ H ₃₈ O ₅ and a molecular weight of 406.

When x is methoxy, the structure is as shown in the formula (3). The chemical name is Antrochinonol C, which has the molecular formula C ₂₅ H ₄₀ O ₅ and a molecular weight of 420.

The Compounds Antroquinonol B and Antroquinone C are by a aqueous extraction or organic solvent extraction isolated from Antrodia camphorata. The organic solvents used include, inter alia, alcohols, such as. As methanol, ethanol or Propanol, esters, such as. For example, ethyl acetate, alkanes, such as. Hexane, or halogenated alkanes, such as. As chloromethane, chloroethane. From These solvents are preferably an alcohol and ethanol is particularly preferred.

The above-mentioned compounds of the present invention can can be used to inhibit tumor cell growth and can as a medical composition for the treatment of cancer and used to enhance the therapeutic effects become. The compounds of the present invention can for inhibiting a number of cancer cells, including Breast cancer, lung cancer, liver cancer and prostate cancer, resulting in a considerable slowdown in the growth of cancer cells leads, and further for inhibiting the proliferation of Cancer cells and to reduce the risk of malignancy be used. Therefore, they can be used to treat Breast cancer, lung cancer, liver cancer, prostate cancer, etc., used become.

on the other hand may be the compounds of formula (2) and / or the formula (3) of the present invention in medical compositions for the treatment of breast cancer, lung cancer, liver cancer and prostate cancer be included to inhibit the growth of tumor cells. The medicinal compositions include not only the effective ones Amounts of antroquinone B and antroquinone C, but also pharmaceutically compatible carriers. The carriers include including vehicle, such as. As water, fillers, such as z. As sucrose or starch, binders, such as. B. cellulose derivatives, Diluent, disintegrant, absorption enhancer or sweetener. The compositions of present invention can be achieved by mixing the compounds Antroquinone B and Antroquinone C with at least one of the carriers by conventional methods used in the technical Field of pharmacy are known, manufactured and among others as a powder, tablet, capsule, pellets, grains or as other, liquid formulation can be formulated.

The The present invention will be described in the following illustrated embodiment and further explained in examples. These below However, examples should not be construed as limiting the scope of protection of the invention, and modifications are intended for the skilled person, the modifications of the essence the invention and the scope of the appended claims are included.

Detailed description of the preferred embodiment

The Mycelia, fruiting bodies or a mixture of both Antrodia camphorata are first with water or organic solvents extracted to the aqueous extract or the organic Solvent extract from Antrod / a camphorata using to obtain known method. The organic solvents include, inter alia, alcohols, such as. As methanol, ethanol or Propanol, esters, such as. For example, ethyl acetate, alkanes, such as. Hexane, or halogenated alkanes, such as. As chloromethane and chloroethane. From These solvents are preferably an alcohol and ethanol is particularly preferred.

The aqueous or organic solvent extracts of Antrodia camphorata were subjected to high performance liquid chromatography (HPLC) for isolation and purification. Each fraction was recovered and used in an anti-tumor test. The effective fractions with antitumor activity were analyzed for composition and further tested against various cancer cells. The approach described above then led to the identification of the compounds antroquinonol B and antroquinonol C for inhibiting the growth of breast cancer, lung cancer, liver cancer, prostate cancer, etc. These compounds from Antrodia camphorata are considered as new compounds, as they are described in any literature or publication have been.

The anti-cancer effects of antroquinonol B and antroquinone C were confirmed by the 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay according to the National Cancer Institute (NCI) antitumour drug screening model for cell survival rates Use of cell lines of breast cancer, lung cancer, liver cancer and prostate cancer tested. The above-mentioned tests have shown that antroquinonol B and antroquinonol C increase the survival rates of breast cancer cell lines (MCF-7 and MDA-MB-231), lung cancer cell lines (A-549), hepatocellular carcinoma cell lines (Hep 3B and Hep G2) and prostate cancer. Cell lines (LNCaP and DU-145) and at the same time showed relatively low half-maximal inhibition concentration (IC ₅₀ ) values. Therefore, antroquinonol B and antroquinonol C can be used for inhibiting cancer cell growth of breast cancer, lung cancer, liver cancer and prostate cancer, and therefore further used for cancer treatment of breast cancer, lung cancer, liver cancer, prostate cancer and the like. The details of the examples are described below.

example 1

Isolation of antroquinone B and antroquinone C

100 g mycelia, fruiting bodies or a mixture of both Antrodia camphorata were placed in a flask. A suitable Amount of water and alcohol (70 to 100% alcohol solution) was added to the flask and it was at least 1 hour at Stirred at 20 to 25 ° C. The solution was filtered through a filter and a 0.45 micron membrane and the filtrate was collected as an extract.

The Filtrate from Antrodia camphorata was subjected to high performance liquid chromatography (HPLC) analysis subjected. The separation was carried out on an RP18 column, the mobile phase consisting of methanol (A) and 0.1 to 0.5% acetic acid (B), with the gradient conditions 0 to 10 min in 95% up to 20% B, 10 to 20 min in 20% to 10% B, 20 to 35 min in 10% up to 90% B, 35 to 40 min in 10% to 95% B at a flow rate of 1 ml / min. The column effluent was monitored by a UV-VIS detector.

The fractions collected at 21.2 to 21.4 min were collected and concentrated to give Antroquinonol B, a product which was a pale yellow powder. The analysis of this product showed the molecular formula C ₂₄ H ₃₈ O ₅ and a molecular weight of 406. Examination of the NMR spectra showed that ¹ H-NMR (CDCl ₃ ) δ (ppm) = 1.21, 1.36, 1 , 67, 1.71, 1.75, 1.94, 2.03, 2.07, 2.22, 2.25, 3.68, 4.05, 5.71 and 5.56, ¹³ C NMR _(CDCl3) δ (ppm) = 12.31, 16.1, 16.12, 17.67, 25.67, 26.44, 26.74, 27.00, 39.71, 39.81, 40.27, 43.34, 59.22, 60.59, 71.8, 120.97, 123.84, 124.30, 131.32, 134.61, 135.92, 138.05, 160, 45 and 197.11.

The fractions collected at 23.7 to 24 min were collected and concentrated to give Antroquinonol C, a product which was a pale yellow powder. The analysis of this product showed the molecular formula C ₂₅ H ₄₀ O ₅ and a molecular weight of 420. Examination of the NMR spectra showed that ¹ H-NMR (CDCl ₃ ) δ (ppm) = 1.21, 1.36, 1 , 67, 1.71, 1.75, 1.94, 2.03, 2.07, 2.22, 2.25, 3.24, 3.68, 4.05, 5.12, 5.50 and 5.61, ¹³ C-NMR (CDCl ₃₎ δ (ppm) = 12.31, 16.1, 16.12, 17.67, 24.44, 26.44, 26.74, 27.00, 37.81, 39.81, 40.27, 43.34, 49.00, 59.22, 60.59, 120.97, 123.84, 124.30, 135.92, 138.05, 160, 45 and 197.12.

The Structures of Antrochinonol B and Antroquinone C were in one Database of chemical compounds compared. There was no connection found with a corresponding structure. Therefore, these connections become considered as new compounds, as they have not been described so far have been.

Example 2

Ex vivo survival test regarding Anti cancer effects

The NCI anticancer drug screening model was used to test the anti-cancer effect of the isolated compounds of Example 1 in the present invention. The isolated antroquinonol B and antroquinone C of Example 1 were added to the culture media of human breast cancer cells, MCF-7 or MDA-MB-231 to test tumor cell survival. This survival test was done with the be knew MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) test carried out. The MCF-7 cell line was derived from primary (early stage) breast cancer cells that are estrogen-sensitive and therefore estrogen-dependent, while MDA-MB-231 is insensitive to estrogen and therefore estrogen-independent, being a difficult tumor a low survival rate.

Of the MTT test is usually used to determine cell proliferation, the percentage of viable cells and cytotoxicity used. 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium (MTT) is a yellow dye that absorbs from the living cells and by succinate tetrazolium reductase in the mitochondes to violet-blue Formazan crystals can be reduced. The Formazanbildung can therefore, used to increase the survival rate of cells to evaluate and determine.

The human breast cancer cells MCF-7 (purchased from Bioresources Collection and Research Center (BCRC) with accession number BCRC60436) and MDA-MB-231 (purchased from National Health Research Institutes (NHRI) with accession number CCRC 60425) were identified in media containing fetal Calf serum, cultured for 24 hours. The proliferated cells were washed once with PBS, then treated with 1X trypsin-EDTA and centrifuged for 5 min at 1200 rpm. The supernatant was discarded and the cell pellet was resuspended by gentle shaking in 10 ml of fresh culture medium. The cells were placed in a 96 well plate. Total ethanol extracts of Antrodia camphorata without purification (the control group), antroquinoneol B or antroquinoneol C (the experimental group) were added to each of the 96 wells at the following concentrations: 30, 10, 3, 1, 0.3, 0.1 and 0, respectively. 03 μg / ml. The cells were incubated for 48 hours at 37 ° C in a 5% CO ₂ incubator. MTT was added at a concentration of 2.5 mg / ml to each well in the dark and incubated for 4 hours, after which 100 μl of lysis buffer was added to stop the reaction. The plates were read on an ELISA reader at a wavelength of 570 nm to determine the survival rates. The half-maximal inhibition concentration (IC ₅₀ ) values were also calculated and reported in Table 1. Table 1 Results of an ex vivo survival test for the inhibition of breast cancer cells rehearse IC ₅₀ (μg / ml) MCF-7 MDA-MB-231 control group Crude extracts of A. camphorata 11.13 25.81 experiment group Antroquinonol B 1.94 8.72 Antroquinonol C 1.17 21.9

It can be seen from the result in Table 1 that antroquinonol B and antroquinonol C can decrease the survival rate of the estrogen-dependent breast cancer cells MCF-7. The IC ₅₀ value of antroquinone B with respect to MCF-7 dropped to 1.94 μg / ml, which was 82.56% lower than that of crude extracts of A. camphorata (11.13 μg / ml). Furthermore, the IC ₅₀ value of antroquinolol C with respect to MCF-7 fell to 1.17 μg / ml, which was 89.49% lower than that of crude extracts of A. camphorata (11.13 μg / ml). Therefore, Antrochinonol B and Antroquinolol C from A. camphorata can be used to inhibit the growth of estrogen-dependent breast cancer cells MCF-7.

On the other hand, antroquinone B and antroquinone C can decrease the survival rate of the estrogen-independent breast cancer cells MDA-MB-231. The IC ₅₀ values of antroquinone B and antroquinone C with respect to MDA-MB-231 were 8.72 μg / ml and 21.9 μg / ml, respectively, which were 66.21% and 15.15% lower than those of Crude extracts of A. camphorata (25.81 μg / ml). The concentration of antroquinone B and antroquinone C required for the half-maximal inhibitory concentration of MDA-MB-231 was reduced with respect to the crude extracts in the control group and a better inhibitory effect was found on antroquinone B. Therefore Antrochinonol B and Antrochinonol C from Antrodia camphorata can be used to inhibit the growth of estrogen-independent breast cancer cells MDA-MB-231.

Example 3

Ex vivo survival test regarding Anti cancer effects

The NCI anticancer drug screening model was also used to test the Anticancer effect of antroquinonol B and antroquinolol C in used in the present invention. The isolated antroquinones Example 1 was the culture media of human lung cancer cells A549 was added to improve survival rates with the MTT assay described above to analyze lung cancer cells.

The human lung cancer cells A549 were purchased from the Bioresources Collection and Research Center (BCRC) of the Food Industry Research and Development Institute, accession number BCRC 60074. A549 cells were cultured in media containing fetal calf serum for 24 hours. The proliferated cells were washed once with PBS, then treated with 1X trypsin-EDTA and centrifuged for 5 min at 1200 rpm. The supernatant was discarded and the cell pellet was resuspended by gentle shaking in 10 ml of fresh culture medium. The cells were placed in a 96 well plate. Total ethanol extracts of Antrodia camphorata without purification (the control group), antroquinoneol B or antroquinoneol C (the experimental group) were added to each of the 96 wells at the following concentrations: 30, 10, 3, 1, 0.3, 0.1 and 0, respectively. 03 μg / ml. The cells were incubated for 48 hours at 37 ° C in a 5% CO ₂ incubator. MTT was added at a concentration of 2.5 mg / ml to each well in the dark and incubated for 4 hours, after which 100 μl of lysis buffer was added to stop the reaction. The plates were read on an ELISA reader at a wavelength of 570 nm to determine the survival rates. The half-maximal inhibition concentration (IC ₅₀ values) was also calculated and reported in Table 2. Table 2 Results of an ex vivo survival test for the inhibition of lung cancer cells rehearse IC ₅₀ (μg / ml) A549 control group Crude extracts of A. camphorata 13.21 experiment group Antroquinonol B 11.9 Antroquinonol C 8.21

From the result in Table 2, it can be seen that antroquinonol B and antroquinonol C can effectively decrease the survival rates of the human lung cancer cell line A549. The IC ₅₀ values of antroquinonol B and antroquinone C with respect to A549 were 11.9 μg / ml and 8.21 μg / ml, respectively, which were 9.92% and 37.85% lower than those of crude extracts of A. camphorata (13.21 μg / ml).

Both antroquinone B and antroquinone C showed reduced IC ₅₀ values with respect to the control group and a better inhibitory effect was found with antroquinone B. Therefore, Antroquinone B and Antroquinone C from A. camphorata can be used to inhibit the growth of lung cancer cells A549.

Example 4

Ex vivo survival test regarding Anti liver cancer effects

The NCI anticancer drug screening model was used to test the anti-cancer effect of Antroquinoneol B and Antroquinonol C in the present invention ver used. The isolated Antrochinonole of Example 1 were the Culture media of human liver cancer cells Hep 3B or Hep G2 added for a tumor cell survival test. The liver cancer cells Hep 3B (BCRC 60434) and Hep G2 (BCRC 60025) were funded by the Bioresources Collection and Research Center (BCRC) of the Food Industry Research and Development Institute.

The human liver cancer cells Hep 3B and Hep G2 were cultured in media containing fetal calf serum for 24 hours. The proliferated cells were washed once with PBS, then with 1X Trypsin-EDTA and centrifuged for 5 min at 1200 rev / min. The supernatant was discarded and the cell pellet was resuspended by gentle shaking in 10 ml of fresh culture medium. The cells were placed in a 96 well plate. Total ethanol extracts of Antrodia camphorata without purification (the control group), antroquinoneol B or antroquinoneol C (the experimental group) were added to each of the 96 wells at the following concentrations: 30, 10, 3, 1, 0.3, 0.1 and 0, respectively. 03 μg / ml. The cells were incubated for 48 hours at 37 ° C in a 5% CO ₂ incubator. MTT was added at a concentration of 2.5 mg / ml to each well in the dark and incubated for 4 hours, after which 100 μl of lysis buffer was added to stop the reaction. The plates were read on an ELISA reader at a wavelength of 570 nm to determine the survival rates. The half-maximal inhibition concentration (IC ₅₀ ) values were also calculated and are given in Table 3. Table 3 Results of an ex vivo survival test for inhibition of liver cancer cells rehearse IC ₅₀ (μg / ml) Hep 3B Hep G2 control group Crude extracts of A. camphorata 5.10 18.63 experiment group Antroquinonol B 1.21 3.32 Antroquinonol C 1.32 5.12

It can be seen from the result in Table 3 that antroquinonol B and antroquinonol C can effectively reduce the survival rates of the human liver cancer cell lines Hep 3B and Hep G2. The IC ₅₀ value of antroquinone B with respect to Hep 3B was 1.21 μg / ml, which was 76.27% lower than that of crude extracts of A. camphorata (5.10 μg / ml). The IC ₅₀ value of antroquinolol C with respect to Hep 3B was 1.32 μg / ml, which was 74.12% lower than that of crude extracts of A. camphorata. Both compounds showed significantly reduced IC ₅₀ values in Hep 3B cells relative to the control group. The IC ₅₀ values of antroquinone B and antroquinone C with respect to Hep G2 were 3.32 μg / ml and 5.12 μg / ml, respectively, which were 82.18% and 72.52% lower than those of crude extracts of A. camphorata (18.63 μg / ml). Both compounds showed significantly reduced IC ₅₀ values in Hep G2 cells relative to the control group. Therefore, Antrochinonol B and Antroquinone C from A. camphorata can be used to inhibit the growth of liver cancer cells.

In addition, liver cancer cells treated with antroquinone B showed lower IC ₅₀ values than cells treated with antroquinone C, ie a lower concentration of antroquinone B was required to inhibit the growth of liver cancer cells Hep 3B and Hep G2. Antroquinonol B has better inhibitory effects on the growth of liver cancer cells than antroquinone C.

Example 5

Ex vivo survival test regarding Anti prostate cancer effects

The NCI anticancer drug screening model was also used to test the Anticancer effect of the antroquinones in the present invention used. Antroquinone B and Antroquinone C, which in the example 2 were isolated from the culture media of human Prostate cancer cells LNCaP or DU-145 added and survival rates of prostate cancer cells were analyzed by the above-mentioned MTT test. LNCaP originated from epithelial cells of the prostate gland, which depend on androgen in the early stage, and consequently, it is an androgen-dependent cancer cell. DU-145 is a prostate cancer cell of the recurrent type, which does not depend on androgen for growth and is therefore androgen-independent. For this Prostate cancer of the recurrent type, there are no effective Treatment. Both LNCaP and DU-145 were approved by the NHRI Accession numbers CCRC 60088 and CCRC 60348 received.

The human prostate cancer cells LNCaP and DU-145 were cultured in media containing fetal calf serum for 24 hours. The proliferated cells were washed once with PBS, then with 1X Trypsin-EDTA and centrifuged for 5 min at 1200 rev / min. The supernatant was discarded and the cell pellet was resuspended by gentle shaking in 10 ml of fresh culture medium. The cells were placed in a 96 well plate. Total ethanol extracts of Antrodia camphorata without purification (the control group), antroquinoneol B or antroquinoneol C (the experimental group) were added to each of the 96 wells at the following concentrations: 30, 10, 3, 1, 0.3, 0.1 and 0, respectively. 03 μg / ml. The cells were incubated for 48 hours at 37 ° C in a 5% CO ₂ incubator. MTT was added at a concentration of 2.5 mg / ml to each well in the dark and incubated for 4 hours, after which 100 μl of lysis buffer was added to stop the reaction. The plates were read on an ELISA reader at a wavelength of 570 nm to determine the survival rates. The half maximal inhibition concentration (IC ₅₀ ) values were also calculated and reported in Table 4. Table 4 Results of an ex vivo survival test for the inhibition of prostate cancer cells rehearse IC ₅₀ (μg / ml) LNCaP DU-145 control group Crude extracts of A. camphorata 11.49 41.39 experiment group Antroquinonol B 5.67 10.12 Antroquinonol C 8.72 12.21

From the result in Table 4, it can be seen that the survival rates of cells of LNCaP and DU-145 were effectively reduced by the activities of antroquinonol B or antroquinone C. The IC ₅₀ values of antroquinonol B and antroquinone C with respect to LNCaP were 5.67 μg / ml and 8.72 μg / ml, respectively, which were 50.65% and 24.11% lower than the IC ₅₀ value of Control group (11.49 μg / ml). The IC ₅₀ values of antroquinonol B and antroquinone C with respect to DU-145 were 10.12 μg / ml and 12.21 μg / ml, respectively, which were 75.55% and 70.5% lower than the IC ₅₀ . Value of the control group (41.39 μg / ml). Therefore, the half-maximal inhibitory concentrations of these two A. camphorata antroquinones were significantly reduced with respect to the prostate cancer cells LNCaP and DU-145 compared to the crude extracts in the control group. In addition, LNCaP prostate cancer cells treated with antroquinone B showed much lower IC ₅₀ values than antroquinone C-treated cells, ie a better inhibitory effect on antroquinone B was found with respect to the inhibition of prostate cancer cells.

on the other hand Both Antrochinonol B and Antroquinone C can increase growth of LNCaP and DU-145 prostate cancer cells with two different Effectively inhibit characteristics. Therefore, Antroquinone B and Antrochinonol C for inhibiting not only the growth of Androgen-dependent prostate cancer cells LNCaP, but also androgen-independent prostate cancer cells DU-145 be used. This is for the treatment of prostate cancer and useful for recurrent prostate cancer.

In summary Antroquinone B and Antroquinone C, which are extracted from extracts isolated from A. camphorata, the growth of breast cancer, Effectively inhibit lung cancer, liver cancer and prostate cancer. These Compounds can be used in medical compositions Treatment of the above-mentioned cancer cells are included. The medicinal compositions not only contain the compounds of Antroquinone B and Antroquinone C, but also pharmaceutically compatible carriers. The carriers include including vehicle, such as. As water, fillers, such as z. As sucrose or starch, binders, such as. B. cellulose derivatives, Diluent, disintegrant, absorption enhancer or sweetener. The inventive Composition can be achieved by mixing the compounds Antrochinonol B and Antroquinolol C with at least one of the carriers by means of conventional methods used in the technical field of pharmacy are known, prepared and, among other things, as a powder, Tablet, capsule, pellets, grains or as other, liquid Formulation be formulated.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited non-patent literature

• - IH Cherng and HC Chiang, 1995, Three new triterpenoids from Antrodia cinnamomea, J. Nat. Prod., 58, 365-371 [0005]
• - Chen et al. [0005]
• - CH Chen and SW Yang, 1995, New steroid acids from Antrodia cinnamomea - a fungus parasitic to Cinnamomum micranthum, J. Nat. Prod. 58, 1655-1661 [0005]
• - Cherng et al. [0005]
• - HC Chiang, DP Wu, IW Cherng, and CH Ueng, 1995, Aspespeneic lactones, phenyl and biphenyl compounds from Antrodia cinnamomea, Phytochemistry, 39, 613-616 [0005]
• - Cherng et al. [0005]
• - IH Cherng, DP Wu and HC Chiang, 1996, Triterpenoids from Antrodia cinnamomea, Phytochemistry 41, 263-267 [0005]
• - Yang et al. [0005]
• - SW Yang, YC Shen and CH Chen, 1996, Steroids and triterpenoids of Antrodia cinnamomea - a fungus parasitic to Cinnamomum micranthum, Phytochemistry 41, 1389-1392 [0005]

Claims (16)

A compound having the following formula wherein x is hydroxyl (-OH) or methoxy (-OCH ₃ ).

A compound according to claim 1, wherein the compound has been isolated from Antrodia camphorata. A compound according to claim 1, wherein the compound Antroquinonol B is when x is hydroxyl (OH). A compound according to claim 3, wherein the compound Antroquinonol B has been isolated from Antrodia camphorata. A compound according to claim 1, wherein the compound is antroquinoneol C when x is methoxy (OCH ₃ ). A compound according to claim 5, wherein the compound Antroquinonol C has been isolated from Antrodia camphorata. A compound according to claim 3 which is for inhibiting the Growth of cancer cells is used, with the cancer cells Breast cancer cells, liver cancer cells or prostate cancer cells. A compound according to claim 7, wherein the breast cancer cells from the group consisting of the breast cancer cell line MCF-7 and breast cancer cell line MDA-MB-231. A compound according to claim 7, wherein the liver cancer cells from the group consisting of the liver cancer cell line Hep 3B and the liver cancer cell line Hep G2. A compound according to claim 7, wherein the prostate cancer cells from the group consisting of the prostate cancer cell line LNCaP and the breast cancer cell line DU-145. Medical composition for inhibition the growth of tumor cells is used, which is a compound according to claim 3 and a pharmaceutically acceptable Carrier comprises, wherein the tumor cells from the group consisting from breast cancer, liver cancer and prostate cancer are. A compound according to claim 5 which is for inhibition The growth of cancer cells is used, with the cancer cells Breast cancer cells, liver cancer cells or prostate cancer cells. The compound of claim 12, wherein the breast cancer cells from the group consisting of the breast cancer cell line MCF-7 and breast cancer cell line MDA-MB-231. The compound of claim 12, wherein the liver cancer cells from the group consisting of the liver cancer cell line Hep 3B and the liver cancer cell line Hep G2. The compound of claim 12, wherein the prostate cancer cells from the group consisting of the prostate cancer cell line LNCaP and the breast cancer cell line DU-145. A medical composition used to inhibit the growth of tumor cells comprising a compound of claim 5 and a pharmaceutically acceptable carrier, wherein the tumor cells are selected from the group consisting of breast cancer, liver cancer and prostate cancer.